Soluble coxsackievirus B3 3C protease inhibitor prevents cardiomyopathy in an experimental chronic myocarditis murine model.

•Re-established the chronic CVB3 myocarditis animal model for drug administration.•Produced water-soluble 3CPI by chemically modifying the water-insoluble 3CPI.•3CPI inhibited virus replication in various organs, myocardial damage, and reduced mortality.•Soluble 3CPI may be beneficial in the treatment of cardiomyopathy associated with enterovirus infection.